Cerebral stroke is the fourth cause of death and leading cause of adult disability. However, current treatments are limited both in terms of utility and effectiveness. Efficacy of stroke interventions are tested using rodent middle cerebral artery occlusion (MCAO) models of focal brain ischemia but these have a substantial impact upon animal suffering/welfare. This PhD will determine if interventions can improve welfare for those rodents undergoing MCAO focusing on three areas:
(I) Use of telemetry to identify intervention and/or humane end points - induction of MCAO results in a hyperthermic response and it is likely that decreased thermoregultion contributes to reduced motility, reduced food/water intake, increased weight loss and increased mortality. This PhD will use telemetry to monitor thermoregulation in rodents following MCAO surgery which will allow the recognition of appropriate time points for intervention and/or humane end points in an attempt to reduce suffering and distress;
(II) Environmental enrichment - post-stroke enrichment has a positive effect on outcome but little consideration has been given to enriching the environment of rodents pre-stroke. This PhD will validate the extent to which enriched housing improves the well-being of rodents generally and following stroke surgery;
(III) Intervention surgery – others have shown the benefit of hypertensive rats undergoing a brief surgical procedure to induce craniotomy prior to MCAO surgery. This led to a significant reduction in oedema formation and significantly improved survival without impacting upon the stroke-specific damage. This PhD project will investigate the benefit of such pre-intervention surgery on 'normal' rodents which are the majority of animals undergoing experimental stroke. Importantly, these studies will be conducted in rats and mice, of both genders, to ensure any improvements in welfare have a significant benefit for the majority of animals undergoing experimental stroke.
Bayliss M et al. (2018). Pre-stroke surgery is not beneficial to normotensive rats undergoing sixty minutes of transient focal cerebral ischemia. PLOS ONE 13(12): e0209370. doi: 10.1371/journal.pone.0209370
- Further Funding: NC3Rs Skills and Knowledge Transfer Grant, Dissemination of refinements in mouse experimental stroke models to the scientific community, August 2017, £65,220
- Further Funding: NC3Rs Pilot Study Grant, Determining the source of variability within experimental stroke models, November 2014, £74,586